Merck Updates on Phase 3 KeyVibe-010 Trial for Vibostolimab and Pembrolizumab in High-Risk Melanoma

Merck, known as MSD outside the United States and Canada, announced the discontinuation of the Phase 3 KeyVibe-010 trial arm involving a coformulation of vibostolimab and pembrolizumab. The trial was assessing this coformulation against pembrolizumab alone in patients with resected high-risk melanoma (Stage IIB-IV). The decision came after a pre-planned analysis showed the primary endpoint of recurrence-free survival (RFS) did not meet the necessary criteria. A higher discontinuation rate in the coformulation arm due to immune-mediated adverse experiences indicated it was unlikely to achieve a significant improvement in RFS. Following the recommendation of an independent Data Monitoring Committee (DMC), Merck is unblinding the study and advising patients in the coformulation arm to switch to KEYTRUDA monotherapy. Data analysis continues, with results to be shared with the scientific community and regulatory agencies.

Dr. Marjorie Green, senior vice president and head of oncology at Merck Research Laboratories, stated that the clinical development program aims to explore novel coformulations and combinations based on KEYTRUDA to improve current cancer care standards. She emphasized the importance of patient and investigator participation, which will inform the ongoing development of new treatment mechanisms, including further investigation of this coformulation in lung cancer.

Merck remains committed to advancing melanoma treatment, especially in earlier disease stages. This commitment is exemplified by the ongoing Phase 3 V940-001 study, in collaboration with Moderna, which evaluates V940 (mRNA-4157), an investigational individualized neoantigen therapy, combined with KEYTRUDA for adjuvant treatment in high-risk melanoma patients.

In the U.S., KEYTRUDA is approved for treating unresectable or metastatic melanoma and as adjuvant therapy for adult and pediatric patients (12 years and older) with stage IIB, IIC, or III melanoma post-resection.

Vibostolimab, Merck's investigational anti-TIGIT antibody, functions by blocking the TIGIT receptor from binding to its ligands, thus activating T cells to attack tumor cells. Merck's clinical development program includes over 3,000 patients evaluating the safety and efficacy of the vibostolimab and pembrolizumab coformulation alone and in combination with other agents. Ongoing Phase 3 studies in lung cancer include KeyVibe-003, KeyVibe-006, KeyVibe-007, and KeyVibe-008. Interim safety reviews from external data monitoring committees have not led to any safety-related modifications in these studies, and no changes are anticipated based on KeyVibe-010 findings.

KeyVibe-010 is a randomized, double-blind, active comparator-controlled Phase 3 trial evaluating the vibostolimab and pembrolizumab coformulation versus KEYTRUDA alone as an adjuvant treatment for high-risk Stage IIB-IV melanoma. The primary endpoint is RFS, with secondary endpoints including distant metastasis-free survival (DMFS) and overall survival (OS). The trial enrolled 1,594 patients who received either the coformulation or pembrolizumab alone. The coformulation was administered intravenously every three weeks for up to 17 cycles.

Melanoma, the most serious form of skin cancer, is characterized by uncontrolled growth of pigment-producing cells. Incidence rates have been increasing, with over 330,000 new cases worldwide in 2022. In the U.S., melanoma is a major cause of skin cancer deaths, with over 100,000 new cases and more than 8,000 deaths expected in 2024.

Merck's early-stage cancer clinical program focuses on detecting cancer at earlier stages, potentially increasing long-term survival. Building on the role of KEYTRUDA in later-stage cancers, the program includes over 25 ongoing registrational studies across various cancer types.

Vibostolimab (MK-7684) is a humanized anti-TIGIT antibody designed to restore antitumor activity by blocking the TIGIT receptor's binding to its ligands, thereby activating T cells to destroy tumor cells. The coformulation of vibostolimab and pembrolizumab is under investigation for various cancers, including lung, other solid tumors, and blood cancers.

KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that enhances the body's immune system to detect and fight tumor cells. It is a humanized monoclonal antibody that blocks PD-1 from interacting with its ligands, thereby activating T cells, which may affect both tumor and healthy cells. Merck's KEYTRUDA clinical program is extensive, with over 1,600 trials across a wide range of cancers and treatment settings. The program aims to understand KEYTRUDA's role in different cancers and identify factors predicting patient response, including various biomarkers.